17q Gain in Neuroblastoma: A Review of Clinical and Biological Implications

Abstract

Neuroblastoma (NB) is the most frequent extracranial solid childhood tumor. Despite advances in the understanding and treatment of this disease, the prognosis in cases of high-risk NB is still poor. 17q gain has been shown to be the most frequent genomic alteration in NB. However, the significance of this remains unclear because of its high frequency and association with other genetic modifications, particularly segmental chromosomal aberrations, 1p and 11q deletions, and MYCN amplification, all of which are also associated with a poor clinical prognosis. This work reviewed the evidence on the clinical and biological significance of 17q gain. It strongly supports the significance of 17q gain in the development of NB and its importance as a clinically relevant marker. However, it is crucial to distinguish between whole and partial chromosome 17q gains. The most important breakpoints appear to be at 17q12 and 17q21. The former distinguishes between whole and partial chromosome 17q gain; the latter is a site of IGF2BP1 and NME1 genes that appear to be the main oncogenes responsible for the functional effects of 17q gain.

The Neuroblastoma Microenvironment, Heterogeneity and Immunotherapeutic Approaches

“…While lower-stage tumors are usually hyperdiploid, high-risk cases frequently contain diploid tumor cells [52]. Among the primary high-risk cases, segmental gain of 17q is the most common aberration, characterizing 90% of tumor samples with gains larger or equal to the minimum region between 17q23.1 and 17qter [48,[53][54][55]. Therefore, genes located in 17q, such as PPM1D, BIRC5, IGF2BP1, and others, are researched as potential initiators or therapeutic targets for neuroblastoma [54][55][56].…”

BPTF cooperates with MYCN and MYC to link neuroblastoma cell cycle control to epigenetic cellular states

“…We hypothesized that BPTF plays a key cooperative role in high-risk neuroblastoma tumorigenesis based on the following: i) MYCN amplification is a major oncogenic driver in this tumor; ii) tumors lacking MYCN amplification often display high-level MYC expression; iii) BPTF might also be required for MYCN transcriptional activity; and iv) the BPTF locus lies on chr. 17q24, a region that shows copy number gain in the vast majority of high-risk neuroblastomas, as well as in other tumors 27, 28, 29 .…”

Extracellular vesicles in neuroblastoma: role in progression, resistance to therapy and diagnostics

“…Importantly, 17q gain is found in more than 50% of all NB cases, and is independently associated with poor survival in patients with advanced-stage-NB ( 11 – 13 ), thus suggesting its clinical significance in NB. Several candidate oncogenes found on this frequently amplified 17q21-ter locus ( 14 ) are being investigated for their relevance in NB progression. One of these candidate oncogenes, IGF2BP1, was shown to promote NB metastasis by altering the function of NB-secreted small extra cellular vesicles (EVs) ( 15 ).…”